PROJECT SUMMARY This multi-site (Vanderbilt University Medical Center [VUMC] and Ohio State University [OSU]) R01 application is submitted in response to PA-18-502--Advancing the Science of Geriatric Palliative Care. This proposal examines the impact of stage 4 breast and prostate cancer on psychophysical measures of pain sensitivity and unpleasantness in Alzheimer's disease (AD). A considerable number of older adults will suffer from cancer and co-occurring AD placing them at great risk of suffering under treated cancer pain. Understanding the impact of cancer and AD on pain perception will provide key insights into cancer pain in AD. Unfortunately, the consequences of untreated cancer pain can be devastating. More than 50% of hospitalized patients with cancer described their pain as `distressing, horrible, or excruciating'. It remains unknown how cancer and Alzheimer's disease alter pain processing. Altered pain processing may further increase the risk for reduced detection of pain upon injury, increase the risk for under treatment of metastatic cancer pain, and may predispose to increased suffering. If our results determine that cancer and co- occurring Alzheimer's disease place these individuals at risk of increased suffering, targeted analgesic drug development strategies, and/or tailored interventions to maximize pain treatment can then be designed for this highly vulnerable and under studied population. We will study thermal and pressure pain thresholds as well as central sensitization (assessed via temporal summation) to pain in 132 people balanced by group at each site (total n=264):132 males (44 with stage 4 prostate cancer, 44 with AD and stage 4 prostate cancer, and 44 with AD only) and 132 females (44 with stage 4 breast cancer, 44 with AD and stage 4 breast cancer, and 44 with AD only). Our overall hypothesis is that when compared to older adults with AD only, older adults with stage 4 breast and prostate cancer pain develop CNS sensitization and are at risk of experiencing intense daily cancer pain, and in those with comorbid AD, brain damage leads to further alterations in CNS pain processing which decreases the ability to recognize and accurately self-report pain, increases the risk of under treatment of cancer pain, and may predispose to increased suffering at the end of life. We have designed the proposed study to minimize the burden of participating in research to make the subjects and their caregivers as comfortable as possible including collecting all study data wherever the participant resides such as home, assisted living, or nursing homes. To summarize, there are extremely few studies examining the impact of cancer and co-occurring Alzheimer's disease on pain perception and there are no controlled experimental studies of pain in this population. The proposed study is the first to test pain threshold and perception in this under-studied population. Results may immediately help guide pain care in this highly vulnerable group of older adults.